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OBJECTIVE: To investigate the extent to which relapse and other previously treated tuberculosis (TB) contribute to the notified TB burden in South Africa. DESIGN: We conducted an ecological analysis at the level of the 52 South African health districts using national electronic TB register data. We included all bacteriologically confirmed TB cases treated for presumed drug-susceptible TB in 2011. Treatment history information was based on recorded patient categories (new vs. retreatment). RESULTS: Relapse and other previously treated TB cases constituted between 7.6% and 40% (median 17%, interquartile range 12-22) of all bacteriologically confirmed TB cases in the 52 South African districts. Multivariable analysis suggested that districts with higher proportions of previously treated TB cases had higher TB case notification rates ( P < 0.001), lower estimates of antenatal human immunodeficiency virus (HIV) prevalence in the district population ( P < 0.001) as well as lower HIV co-infection rates ( P < 0.001) among new TB cases. CONCLUSION: Relapse and other previously treated TB cases contributed substantially to the notified TB burden in several South African health districts, particularly those with high case notification rates and lower antenatal HIV prevalence. Additional efforts to prevent TB among previously treated people, such as strengthening treatment monitoring and/or secondary preventive therapy, should be considered.

Background: Smear-positive patients should be started on anti-tuberculosis treatment promptly. However, studies show that up to 38% of diagnosed patients are initial loss to follow-up (LTFU), meaning they do not start treatment after diagnosis. We investigated determinants of initial LTFU at primary health care facilities., Design: In a facility-matched case-control study, health care facilities were visited from October 2010 to September 2012. After identification from registers, patients were traced and invited to complete a questionnaire., Results: Of 973 participants, 233 (24%) were cases and 740 (74%) controls. Initial LTFU was associated with smear grade (pooled adjusted odds ratio [aOR] 0.73, 95% confidence interval [CI] 0.64-0.90, scanty at baseline) for participants identified at facilities, but not with age (overall P = 0.80) or sex (aOR 0.83, 95%CI 0.58-1.20). Of the 233 cases, 197 (85%) were traced in the community, of whom 58 (29%) were found. Among the group found, initial LTFU was associated with age (aOR 3.38, 95%CI 1.15-9.95) and smear grade (aOR 0.08, 95%CI 0.02-0.34, scanty at baseline)., Conclusion: Scanty smear positivity was associated with initial LTFU. Tuberculosis programmes should start scanty smear-positive patients on treatment early and develop alternative community tracing strategies. Health care worker training could address the first aspect, and the use of technology to improve treatment initiation, such as mobile phone applications, the second.

Background: Despite recognised treatment strategies, mortality associated with tuberculosis (TB) remains significant. Risk factors for death during TB treatment have been described but the complex relationship between TB and HIV has not been fully understood., Methods: A retrospective analysis of all deaths occurring during TB treatment in Cape Town, South Africa between 2009 and 2012 were done to investigate risk factors associated with this outcome. The main risk factor was HIV status at the start of treatment and its interaction with age, sex and other risk factors were evaluated using a binomial regression model and thus relative risks (RR) are reported., Results: Overall in the 93,133 cases included in the study 4619 deaths (5%) were recorded. Across all age groups HIV-positive patients were more than twice as likely to die as HIV-negative patients, RR = 2.19 (95% CI: 2.03-2.37). However in an age specific analysis HIV-positive patients 15-24 and 25-34 years old were at an even higher risk of dying than HIV-negative patients, RR = 4.82 and RR = 3.76 respectively. Gender also modified the effect of HIV- with positive women having a higher risk of death than positive men, RR = 2.74 and RR = 1.94 respectively., Conclusion: HIV carries an increased risk of death in this study but specific high-risk groups pertaining to the impact of HIV are identified. Innovative strategies to manage these high risk groups may contribute to reduction in HIV-associated death in TB patients.

Setting: Cape Town, South Africa., Objective: To improve the reading of chest X-rays (CXRs) in child tuberculosis (TB) suspects., Design: We designed a reporting and recording form to assist in the diagnosis of childhood TB from CXRs. We then developed an image bank of antero-posterior and lateral CXR pairs, with each image pair assigned to one of four diagnostic categories. Finally, we designed and carried out a 1-day training course to teach clinicians how to read paediatric CXRs, with pre- and post-course assessments., Results: Of the 27 participants included, 17 (63%) were women. The median age was 38 years (interquartile range [IQR] 32.5-43.5). The median pre-training score was 16.0/30 (IQR 13.0-18.0) and the median post-training score was 17.0 (IQR 13.5-21.0). Sensitivity (P = 0.09) and specificity (P = 0.06) to detect TB did not change as a result of the course; however, the Wilcoxon signed ranks paired-sample test indicated an increase in the participants' overall ability to read CXRs (P = 0.017)., Conclusions: Teaching clinicians with a 1-day training course using a systematic approach and a standardised form led to a limited improvement in CXR reading ability.

Background: The combined tuberculosis (TB) and HIV epidemics in South Africa (SA) have created enormous operational challenges for a health service that has traditionally run vertical programmes for TB treatment and antiretroviral therapy (ART) in separate facilities. This is particularly problematic for TB/HIV co-infected patients who need to access both services., Objective: To determine whether integrated TB facilities had better TB treatment outcomes than single-service facilities in Cape Town, SA., Methods: TB treatment outcomes were determined for newly registered, adult TB patients (aged > or = 18 years) at 13 integrated ART/TB primary healthcare (PHC) facilities and four single-service PHC facilities from 1 January 2009 to 30 June 2010. A chi2 test adjusted for a cluster sample design was used to compare outcomes by type of facility., Results: Of 13,542 newly registered patients, 10,030 received TB treatment in integrated facilities and 3,512 in single-service facilities. There was no difference in baseline characteristics between the two groups with HIV status determined for 9,351 (93.2%) and 3,227 (91.9%) patients, of whom 6 649 (66.3%) and 2,213 (63%) were HIV-positive in integrated facilities and single-service facilities, respectively. The median CD4+ count of HIV-positive patients was 152 cells/microl (interquartile range (IQR) 71-277) for integrated facilities and 148 cells/microl (IQR 67-260) for single-service facilities. There was no statistical difference in the TB treatment outcome profile between integrated and single-service facilities for all TB patients (p = 0.56) or for the sub-set of HIV-positive TB patients (p = 0.58) CONCLUSION: This study did not demonstrate improved TB treatment outcomes in integrated PHC facilities and showed that the provision of ART in the same facility as TB services was not associated with lower TB death and default rates.

Setting: Two paediatric hospitals in Cape Town, South Africa., Objective: To investigate the incidence of and risk factors for severe liver injury in human immunodeficiency virus (HIV) infected children receiving long-term isoniazid preventive therapy (IPT)., Design: Randomised trial of IPT or placebo given daily or thrice weekly to HIV-infected children aged ≥8 weeks; placebo was discontinued early. Alanine transaminase (ALT) was measured at baseline, 6-monthly and during illness: an increase of ≥10 times the upper limit of normal defined severe liver injury., Results: Of 324 children enrolled, 297 (91.6%) received IPT (559.1 person-years [py]). Baseline median age was 23 months (interquartile range [IQR] 9.5-48.6) and median CD4%, 20% (IQR 13.6-26.9). A total of 207 (63.9%) children received combination antiretroviral therapy: 19 developed severe liver injury, 16 while receiving IPT. Among these there were 8 cases of viral hepatitis (5 with hepatitis A), 2 antiretroviral-induced liver injuries and 1 case of abdominal tuberculosis. IPT-related severe liver injury occurred in 1.7% (5/297, 0.78/100 py). No child developed hepatic failure; one died of an unrelated cause. All surviving children subsequently tolerated IPT., Conclusions: This study suggests that long-term IPT has a low toxicity risk in HIV-infected children. In the absence of chronic viral hepatitis, IPT can be safely re-introduced following recovery from liver injury.

Setting: An urban primary health care facility in Khayelitsha, South Africa., Objectives: To determine the difference in total tuberculosis (TB) treatment delay in patients who initially seek care at National TB Control Programme (NTP) facilities after the onset of TB-related symptoms, compared to patients who initially seek care from non-NTP health care practitioners (HCP); and to describe the relative contributions of diagnostic, treatment initiation, patient and health system (HS) delay., Design: A cross-sectional study of adult TB patients treated by the NTP., Results: A total of 210 patients (median age 31 years) were enrolled from May to December 2009: 46% were male, and 58% were human immunodeficiency virus (HIV) infected. The median duration of total delay was 31 days, diagnostic delay 26, treatment initiation delay 0, patient delay 8 and HS delay 17 days. Initial visit to a non-NTP HCP was independently associated with total (P = 0.007), HS (P = 0.014) and diagnostic delays (P = 0.012). HIV infection was an independent risk factor for total (P = 0.047) and HS delay (P = 0.021); 27% of patients reported first going to a non-NTP HCP., Conclusion: Initial care sought from non-NTP HCP was the main determinant of total, HS and diagnostic delays. Engagement and education of private HCPs is recommended.

Background: Reliable surveillance is essential for any tuberculosis (TB) control programme; however, under-registration of TB cases due to under-notification of patients on treatment or failure to initiate treatment has been well-documented internationally., Objective: To determine the contribution of capture-recapture methods in estimating the completeness of bacteriologically confirmed pulmonary TB registration in two high-incident communities in South Africa., Methods: Record linkage between the TB treatment register and two laboratory sputum TB result registers and three-source log-linear capture-recapture analysis., Results: The number of bacteriologically confirmed pulmonary TB cases in the TB treatment register was 243, with an additional 63 cases identified in the two laboratory databases, resulting in 306 TB cases. The observed completeness of the TB treatment register was 79%. The log-linear model estimated 326 (95%CI 314-355) TB cases, resulting in an estimated completeness of registration of 75% (95%CI 68-77)., Conclusion: Capture-recapture can be useful in evaluating the completeness of TB control surveillance and registration, including in resource-limited settings; however, methodology and results should be carefully assessed. Interventions are needed to increase the completeness of registration and to reduce the number of initial defaulters.

Background: Tuberculosis (TB) is a major cause of morbidity and mortality among children infected with HIV. Strategies to prevent TB in children include isoniazid preventive therapy (IPT) and antiretroviral therapy (ART). IPT and ART have been reported to reduce TB incidence in adults but there are few studies in children., Objective: To investigate the combined effect of IPT and ART on TB risk in children infected with HIV., Methods: A cohort analysis was done within a prospective, double-blinded, placebo-controlled trial of isoniazid (INH) compared with placebo in children infected with HIV in Cape Town, South Africa, a high TB incidence setting. In May 2004 the placebo arm was terminated and all children were switched to INH. ART was not widely available at the start of the study, but children were started on ART following the establishment of the national ART program in 2004. Data were analysed using Cox proportional hazard regression., Results: After adjusting for age, nutritional status and immunodeficiency at enrolment, INH alone, ART alone and INH combined with ART reduced the risk of TB disease by 0.22 (95% CI 0.09 to 0.53), 0.32 (95% CI 0.07 to 1.55) and 0.11 (95% CI 0.04 to 0.32) respectively. INH reduced the risk of TB disease in children on ART by 0.23 (95% CI 0.05 to 1.00)., Conclusions: The finding that IPT may offer additional protection in children on ART has significant public health implications because this offers a possible strategy for reducing TB in children infected with HIV. Widespread use of this strategy will however require screening of children for active TB disease. Trial registration Trial registration-Clinical Trials NCT00330304.

Objective: To investigate whether PALSA PLUS, an on-site educational outreach programme of non-didactic, case based, iterative clinical education of staff, led by a trainer, can increase access to and comprehensiveness of care for patients with HIV/AIDS., Design: Cluster randomised trial., Setting: Public primary care clinics offering HIV/AIDS care, antiretroviral treatment (ART), tuberculosis care, and ambulatory primary care in Free State province, South Africa., Participants: Fifteen clinics all implementing decentralisation and task shifting were randomised. The clinics cared for 400,000 general primary care patients and 10,136 patients in an HIV/AIDS/ART programme. There were 150 nurses., Intervention: On-site outreach education in eight clinics; no such education in seven (control)., Main Outcome Measures: Provision of co-trimoxazole prophylaxis among patients referred to the HIV/AIDS/ART programme, and detection of cases of tuberculosis among those in the programme. Proportion of patients in the programme enrolled through general primary care consultations., Results: Patients referred to the HIV/AIDS programme through general primary care at intervention clinics were more likely than those at control clinics to receive co-trimoxazole prophylaxis (41%, (2253/5523) v 32% (1340/4210); odds ratio 1.95, 95% confidence interval 1.11 to 3.40), and tuberculosis was more likely to be diagnosed among patients with HIV/AIDS/ART (7% (417/5793) v 6% (245/4343); 1.25, 1.01 to 1.55). Enrolment in the HIV/AIDS and ART programme through HIV testing in general primary care was not significantly increased (53% v 50%; 1.19, 0.51 to 2.77). Secondary outcomes were similar, except for weight gain, which was higher in the intervention group (2.3 kg v 1.9 kg, P<0.001)., Conclusion: Though outreach education is an effective and feasible strategy for improving comprehensiveness of care and wellbeing of patients with HIV/AIDS, there is no evidence that it increases access to the ART programme. It is now being widely implemented in South Africa., Trial Registration: Current Controlled Trials ISRCTN 24820584.

Background: Although tuberculosis (TB) treatment registers and laboratory records are essential tools for recording and reporting in TB control programmes, the accuracy and completeness of routinely collected data are seldom monitored., Objective: To assess the accuracy and completeness of TB treatment register data in two South African urban communities using record linkage., Methods: All cases of bacteriologically confirmed TB, defined as two smear-positive results and/or at least one culture-positive result, were included. Record linkage was performed between three data sources: 1) TB treatment registers, 2) the nearest central laboratory, and 3) the referral hospital laboratory., Results: The TB treatment registers had 435 TB cases recorded, of which 204 (47%) were bacteriologically confirmed. An additional 39 cases recorded as non-bacteriological cases in the TB treatment registers were reclassified as bacteriologically confirmed, and 63 bacteriologically confirmed cases were identified from the laboratory databases that were not recorded in the TB treatment registers. The final number of bacteriologically confirmed TB cases was 306, giving an increase of 50%., Conclusions: The accuracy and completeness of the TB treatment register and central laboratory data were inadequate. A high percentage of bacteriologically confirmed cases from both laboratories were not recorded in the TB treatment registers. We are developing an electronic result management system to improve the management of laboratory results.

Background: It is unclear whether human immunodeficiency virus (HIV) increases the risk of tuberculosis (TB) mainly through reactivation or following recent Mycobacterium tuberculosis (re)infection. Within a DNA fingerprint-defined cluster of TB cases, reactivation cases are assumed to be the source of infection for subsequent secondary cases. As HIV-positive TB cases are less likely to be source cases, equal or higher clustering in HIV-positives would suggest that HIV mainly increases the risk of TB following recent infection., Methods: A systematic review was conducted to identify all studies on TB clustering and HIV infection in HIV-endemic populations. Available individual patient data from eligible studies were pooled to analyse the association between clustering and HIV., Results: Of seven eligible studies, six contributed individual patient data on 2116 patients. Clustering was as, or more, likely in the HIV-positive population, both overall (summary OR 1.26, 95%CI 1.0-1.5), and within age groups (OR 1.50, 95%CI 0.9-2.3; OR 1.00, 95%CI 0.8-1.3 and OR 2.57, 95%CI 1.4-5.7) for ages 15-25, 26-50 and >50 years, respectively., Conclusions: Our results suggest that HIV infection mainly increases the risk of TB following recent M. tuberculosis transmission, and that TB control measures in HIV-endemic settings should therefore focus on controlling M. tuberculosis transmission rather than treating individuals with latent M. tuberculosis infection.

Setting: Public sector primary care clinics in Free State Province, South Africa., Objectives: To investigate the effects of on-site in-service clinical skills training for nurse practitioners on tuberculosis (TB) treatment outcomes in the same clinics., Design: Analysis of TB programme data from clinics taking part in two consecutive randomised trials of educational outreach aimed at improving respiratory and human immunodeficiency virus/acquired immune-deficiency syndrome care based on the Practical Approach to Lung Health. We compared treatment outcomes between control and intervention clinics among all patients diagnosed with TB during either trial., Results: During the two trials, participating clinics treated 4187 and 2333 TB patients, respectively. Neither intervention was associated with better outcomes overall. However, among retreatment patients, cure or completion rates in intervention clinics were significantly higher during the second trial (OR 1.78, 95%CI 1.13-2.76). Patients in clinics that had received both interventions had higher cure or completion rates (OR 1.99, 95%CI 1.53-2.58) and lower default rates (OR 0.25, 95%CI 0.097-0.63) than patients in clinics that had received neither intervention., Conclusion: Although not primarily focused on TB treatment, the interventions appeared to improve successful treatment completion rates among TB retreatment cases. Integrated care programmes support attainment of important TB programme goals.

Passive detection of tuberculosis (TB) cases may lead to delay in treatment which may contribute to increased severity of disease and mortality. Active case finding may be an alternative. In a community survey in Cape Town, South Africa, we actively detected 27 bacteriologically positive TB cases and compared those with 473 passively detected TB cases. Seven of 27 (26%) actively detected TB cases did not start treatment within 2 months and were considered initial defaulters. Those who did start treatment had similar treatment success rates as passively detected TB cases (both 80%) (OR 1.01, CI 0.33-3.09). Passively detected cases reported the presence of the symptoms cough (OR 3.72, 95% CI 1.47-9.39), haemoptysis (OR 3.20, 95% CI 1.03-9.93), night sweats (OR 3.35, 95% CI 1.40-7.99), fever (OR 4.28, 95% CI 1.21-15.14), and weight loss (OR 11.14, 95% CI 4.17-29.74) more often than those detected actively. We conclude that although TB cases detected by a community survey are less symptomatic and are prone to a high initial default rate, active case finding can potentially identify a substantial portion of the existing caseload at an earlier stage of disease, thereby reducing the risk of transmission.

Setting: Thirteen primary health care (PHC) facilities in the Stellenbosch District, South Africa., Objective: To assess the use of a sputum register to evaluate the tuberculosis (TB) diagnostic process and the initiation of TB treatment in selected PHC facilities in a country with a centralised laboratory system., Design: This prospective study was conducted between April 2004 and March 2005. The names of all individuals submitting sputum samples for TB testing were noted in a newly introduced sputum register. We classified all TB suspects with two positive smears as TB cases and consulted TB treatment registers until 3 months after sputum submission to determine how many had started treatment., Results: A total of 4062 persons aged > or =15 years submitted sputum samples, of whom 2484 were TB suspects. There were 2037 suspects with at least two results, 367 (18%) had at least two positive smears and 64 (17%) of these did not start treatment (initial defaulters). Over the entire diagnostic process, up to 5% of TB cases were missed, and up to 26% did not start treatment and were not reported., Conclusion: By correcting diagnostic weaknesses identified in the sputum register, PHC facilities will be able to detect, treat and cure a higher percentage of TB patients.

Background: Epidemiological relation of intestinal helminth infection and atopic disease, both associated with a T-helper (Th) 2 immune response, is controversial, as it has been reported that helminth infection may either suppress or pre-dispose to atopic disease. This relation has not been tested in an area with a high burden of Mycobacterium tuberculosis (MTB) infection, a known Th1-stimulating infection., Objective: To study the association of intestinal helminth infection and atopic disease in a community where helminth infection is endemic and MTB infection is high., Methods: Three-hundred and fifty-nine randomly selected children aged 6-14 years from a poor urban suburb were tested with allergy questionnaire, skin prick test (SPT) to common aeroallergens, Ascaris-specific IgE (Ascaris-sIgE), fecal examination for pathogenic intestinal helminths and tuberculin skin testing (TST). Histamine bronchoprovocation was tested in the group of children aged 10 years and older., Results: were corrected for demographic variables, socioeconomic status, parental allergy, environmental tobacco smoke (ETS) exposure in the household, recent anthelminthic treatment and for clustering in the sampling unit. Results Ascaris-sIgE was elevated in 48% of children, Ascaris eggs were found in 15% and TST was positive in 53%. Children with elevated Ascaris-sIgE had significantly increased risk of positive SPT to aeroallergens, particularly house dust mite, atopic asthma (ever and recent), atopic rhinitis (ever and recent) and increased atopy-related bronchial hyper-responsiveness. In children with negative TST (<10 mm), elevated Ascaris-sIgE was associated with significantly increased risk of atopic symptoms (adjusted odds ratio (OR(adj)) 6.5; 95% confidence interval (CI) 1.9-22.4), whereas in those with positive TST (>/=10 mm) this association disappeared (OR(adj) 0.96; 95% CI 0.4-2.8)., Conclusions: These results suggest that immune response to Ascaris (Ascaris-sIgE) may be a risk factor of atopic disease in populations exposed to mild Ascaris infection and that MTB infection may be protective against this risk, probably by stimulation of anti-inflammatory networks.

Background: Epidemiological studies have shown an inverse relation of mycobacterial infection and the frequency of allergic diseases and asthma. Recent evidence suggests that allergic inflammation may be inhibited in the presence of chronic and persistent infections, such as that by Mycobacterium tuberculosis (MTB). The relation of tuberculin skin test (TST) size, an accepted marker of MTB infection and the frequency of allergic disease symptoms has not been reported from an area where MTB infection is endemic., Objective: To investigate the association of TST and allergic disease symptoms, in children living in a tuberculosis (TB) endemic area., Methods: In this cross-sectional study, 841 children aged 6-14 years from randomly selected household addresses in two poor communities of Cape Town, South Africa, were investigated with TST and standardized International Study on Asthma and Allergies in Childhood-based questionnaire on allergic disease symptoms., Results: Children with positive TST (> or =10 mm) were significantly less likely to have allergic disease symptoms, in particular allergic rhinitis (AR) (adjusted odds ratio 0.43; 95% confidence interval 0.24-0.79) than those with negative TST. This association remained significant after adjusting for possible confounders and correcting for the effect of clustering (>1 child per household address) in the sample. There was a significant inverse linear trend in the relation of TST size in millimetre and the frequency of allergic disease symptoms, in particular AR (P<0.001)., Conclusions: These results of inverse association of strong TST reaction and allergic disease symptoms in children from a TB endemic area are in support of the hypotheses that allergic inflammation may be inhibited by chronic infections, such as MTB.

Background: The association between Mycobacterium tuberculosis (MTB) infection and atopy remains controversial., Aim: To investigate the association between MTB infection and atopic rhinitis in children living in a high TB incidence area., Methods: In this cross-sectional study 418 children aged 6-14 years from an established epidemiological research-site in a poor urban community were invited to participate. They were assessed for allergic rhinitis (ISAAC questionnaire) and skin responses to tuberculin and eight environmental allergens. The presence of a BCG scar was documented, intestinal parasites and total and Ascaris lumbricoides-specific IgE levels were measured. Atopic rhinitis was defined, using the new World Allergy Organization (WAO) definition, as reported allergic rhinitis and a positive skin prick test (SPT > or =3 mm) to any allergen., Results: Among the 337 children enrolled 10.4% had allergic rhinitis, 17.5% a positive SPT and 53% a positive tuberculin skin test (TST > or =10 mm). Children with a positive TST were significantly less likely to have recent atopic rhinitis (OR(adjusted) 0.06; 95% CI 0.007-0.5) than those with a negative TST. SPTs were significantly more common in children with negative TST who had recent allergic rhinitis (OR(adj) 34.0; 95% CI 7.6-152.6), but not in children with positive TST and recent allergic rhinitis (OR(adj) 0.6; 95% CI 0.07-5.2)., Conclusions: MTB infection seems to reduce the prevalence of atopic rhinitis, and influences SPT reactivity in children with allergic rhinitis from a high TB incidence area.

Background: Associations between smoking and tuberculosis disease including death from tuberculosis have been reported, but there are few reports on the influence of smoking on the risk of developing Mycobacterium tuberculosis infection. The aim of this study was to determine the association between smoking and M tuberculosis infection., Methods: In a cross sectional population survey, data on smoking and tuberculin skin test (TST) results of 2401 adults aged > or =15 years were compared., Results: A total of 1832 (76%) subjects had a positive TST (> or = 10 mm induration). Of 1309 current smokers or ex-smokers, 1070 (82%) had a positive TST. This was significantly higher than for never smokers (unadjusted OR 1.99, 95% confidence interval (CI) 1.62 to 2.45). A positive relationship with pack-years was observed, with those smoking more than 15 pack-years having the highest risk (adjusted OR 1.90, 95% CI 1.28 to 2.81)., Conclusion: Smoking may increase the risk of M tuberculosis infection.

Setting: Study conducted in a suburb of Cape Town, South Africa., Objective: Comparison of successful tuberculosis treatment outcome rates between self supervision, supervision by lay health worker (LHW), and supervision by clinic nurse., Methods: Open, randomised, controlled trial with intention-to-treat analysis., Results: All groups (n = 156) achieved similar outcomes (LHW vs. clinic nurse: risk difference 17.2%, 95% confidence interval [CI] -0.1-34.5; LHW vs. self supervision 15%, 95%CI -3.7-33.6). New patients benefit from LHW supervision (LHW vs clinic nurse: risk difference 24.2%, 95%CI 6-42.5, LHW vs. self supervision 39.1%, 95%CI 17.8-60.3) as do female patients (LHW vs. clinic nurse 48.3%, 95%CI 22.8-73.8, LHW vs. self supervision 32.6%, 95%CI 6.4-58.7)., Conclusions: LHW supervision approaches statistically significant superiority, but fails to reach it most likely due to the study's limitation, the small sample size. It is possible that subgroups (new and female patients) do well under LHW supervision. LHW supervision could be offered as one of several supervision options within TB control programmes.

Objective: To estimate the incidence rate of tuberculosis in HIV-1-infected adults resident in a region with a high tuberculosis prevalence and to identify clinical and laboratory parameters associated with increased risk of developing tuberculosis., Methods: Adult patients going to the University of Cape Town HIV clinics between January 1986 and May 1996. The following variables were assessed for the risk of developing tuberculosis: ethnicity, employment and education status, World Health Organization (WHO) clinical stage, erythrocyte sedimentation rate (ESR), CD4+ count, and total lymphocyte count. Tuberculin skin test data were not available., Results: There were 198 prevalent and 144 incident cases of tuberculosis in the cohort of 1206 patients. The incidence rate of tuberculosis risk was 10.4/100 person years. WHO clinical stages 3 and 4 (risk ratio [RR], 3.4; 95% confidence interval [CI], 1.8-6.4), ESR >75 mm/hour (RR, 3.5; CI, 1.8-6.5) and being a member of a high-prevalence tuberculosis community (RR, 2.5; CI, 1.2-5.1) were independently associated with the risk of developing tuberculosis., Conclusions: HIV-infected adults in Cape Town are at high risk of developing tuberculosis irrespective of tuberculin skin testing. The risk increases markedly with HIV disease progression. Patients at extremely high risk can be identified on the basis of demographic and clinical features. Such individuals would be suitable for targeted tuberculosis prophylaxis.

The relative contribution of reactivated and recently acquired tuberculosis to the disease burden in developing countries is unknown, as are the settings within which most transmission occurs. In an attempt to answer these questions, we combined molecular techniques (restriction fragment length polymorphism analysis) and conventional epidemiology (risk factor analysis and contact tracing) to study 246 consecutive cases of smear-positive tuberculosis in rural South Africa. We estimate that 29-43% of the cases were recently acquired, as they were clustered. We were unable to identify firm transmission links between 73% of clustered cases. Our findings suggest that most smear-positive tuberculosis in rural Africa is both recently acquired and casually transmitted. Tuberculosis control may depend more on promoting early presentation, rapid diagnosis and vaccine development than on chemotherapy.

Setting: Two adjacent Cape Town Local Authority health clinics in Cape Town, South Africa, were selected. Clinic A was designated the 'intervention clinic' and Clinic B the 'control clinic.', Objective: To assess whether the combined strategy of a patient-centred interview plus the issuing of a patient education booklet would have the effect of increasing the adherence of notified pulmonary tuberculosis (TB) patients to prescribed treatment., Design: A controlled intervention study was implemented using a cohort of the first 60 consecutive patients notified with pulmonary TB at both Clinic A and Clinic B; the patient cohort thus consisted of 120 patients., Results: The risk of patient non-adherence to anti-tuberculosis treatment was significantly reduced at the intervention clinic compared to the control clinic., Conclusion: The results of this study indicate the need for further operational research to assist health providers in developing standardised protocols of health education to enhance adherence to treatment in patients who require protracted treatment regimens.

Setting: A voluntary health worker project (Operation Elsies River) was started in a high incidence tuberculosis (TB) area in the Western Cape of South Africa, in order to assist the local TB Control programme with case-holding., Objective: To evaluate the effectiveness of this group of volunteers in enhancing adherence of notified TB patients to tuberculosis treatment., Design: A cohort study was conducted with 351 TB patients (203 children and 148 adults)., Results: The data from the child and the adult groups were analysed separately. The child group was more adherent to TB treatment than adults. The supervision option with staff dedicated to the treatment of TB, such as the clinic and the SANTA crèche, achieved better adherence results for pre-school children. The supervision modalities for adults did not differ in their adherence performance even following adjustment for confounders., Conclusion: The supervision option provided by the volunteers did not significantly improve the adherence of adult patients to antituberculosis treatment.

Objectives: Drug resistance is a serious problem in the treatment of tuberculosis and a threat to successful tuberculosis control programmes. Local health workers have expressed concern that the increasing tuberculosis epidemic in the Western Cape is partly attributable to drug resistance. The aim of this study was to determine the prevalence of tuberculosis drug resistance (including multidrug resistance) and to investigate possible relationships between drug resistance and patient demographic characteristics., Design, Setting, Subjects, Outcome Measures: During a defined period, all adult (> or = 15 years) patients with pulmonary tuberculosis (confirmed by culture) from all tuberculosis clinics in the Western Cape were included. Previous tuberculosis treatment history was obtained by interviews, utilising a standardised questionnaire. Acquired drug resistance was determined on cultures from patients with a prior history of tuberculosis treatment, while initial resistance was determined from tuberculosis cases with no history of previous treatment., Results: Data from 7,266 patients were analysed. After adjusting for missing information by way of a random sample validation study, 32% of patients were found to have a history of previous treatment, 63% indicated no previous treatment, and in 5% the treatment history was unknown. Rates for initial resistance were found to be low at 3,9% for isoniazid, 1,1% for rifampicin and 0,2% for ethambutol. Combined resistance to isoniazid and rifampicin (multidrug resistance) was found to be 1,1% in patients not treated before. Acquired resistance rates were higher at 10,8% for isoniazid, 4,2% for rifampicin, 0,3% for ethambutol and 4,0% for multidrug resistance. Logistic regression analysis of the data indicated that drug resistance was not influenced by population group, gender or age. Patients with a history of tuberculosis treatment were found to be at an increased risk of developing drug resistance (relative risk 2,6). Some regions in the Western Cape had higher proportions of previously treated patients with consequent higher acquired resistance rates., Conclusions: Results from this study indicated that drug resistance is currently not a major problem in the Western Cape, rates comparing favourably with those reported from developed countries and being much lower than those for developing countries. Every effort should therefore be made to maintain the status quo and to prevent the emergence of further resistance. The priority for tuberculosis control in the Western Cape should remain to limit transmission of the disease by reducing the infectious pool through improved cure of (especially) smear-positive cases.

Setting: Two samples of hospitalised tuberculosis (TB) patients were randomly selected., Objective: To evaluate the usefulness of two alcohol-use screening instruments (AUDIT and CAGE)., Design: A cross-sectional analytic study was conducted with 122 patients (61 Coloured and 61 African)., Results: In the coloured group, AUDIT and CAGE identified 57% and 62% of patients respectively as scoring above the cut-off points for possible alcohol misuse. In the African group, AUDIT and CAGE identified 36% and 31% of patients respectively as scoring above the cut-off points. Rates for risky drinking found in community-based studies were lower than those found in this study for the Coloured sample. The male African group's CAGE result for alcohol misuse (17/46; 37%) is similar to the CAGE finding for African male mineworkers (33%), also findings from a community study in African males (34-37%). Both instruments were in agreement with each other for both groups. Slight to substantial agreement was observed between the instruments and other assessments of alcohol misuse (ward sister's perception, patient's file, self-perception and communal drinking), as well as between these assessments, for both groups., Conclusion: Screening instruments such as AUDIT and CAGE can play a useful role in describing alcohol misuse among TB patients and in facilitating intervention programmes.